OmniVira

Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species.

Ruoke Wang1,2 Qi Zhang3 Jiwan Ge4 Wenlin Ren5,6 Rui Zhang3 Jun Lan4 Bin Ju7,8,9 Bin Su10 Fengting Yu11 Peng Chen3 Huiyu Liao10 Yingmei Feng10 Xuemei Li10 Xuanling Shi3 Zheng Zhang7,8,9 Fujie Zhang11 Qiang Ding5,6 Tong Zhang12 Xinquan Wang13 Linqi Zhang1,14,15
Affiliations 15 institutions
  1. NexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Disease Research, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China
  2. Tsinghua-Peking Joint Center for Life Sciences, Beijing 100084, China.
  3. NexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Disease Research, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China.
  4. The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  5. Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing 100084, China
  6. Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.
  7. Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital
  8. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, Guangdong Province, China
  9. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
  10. Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
  11. Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8, Jing Shun Dong Jie, Chaoyang, 100015 District Beijing, China.
  12. Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. Electronic address: [email protected].
  13. The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: [email protected].
  14. Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
  15. Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China. Electronic address: [email protected].
PMID34166623 DOI10.1016/j.immuni.2021.06.003 Year2021 Journal Immunity Languageeng Statusppublish

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the global pandemic and may facilitate escape from current antibody therapies and vaccine protection. Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape. B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. Our results demonstrate major antigenic shifts and potential broadening of the host range for B.1.351 and P.1 variants, which poses serious challenges to current antibody therapies and vaccine protection.

Supporting text Virus Host Location
antibody 9 immune escape 5 neutralization 9 SARS-CoV-2 550 variant of concern 5 Immune Evasion 25 Angiotensin-Converting Enzyme 2 177 Animals 1948 Antibodies, Monoclonal 26 Antibodies, Neutralizing 80 Antigenic Variation 14 COVID-19 425 Host Specificity 132 Humans 1440 Mice 253 Mink 48 Mutation 209 Protein Binding 193 SARS-CoV-2 453 Spike Glycoprotein, Coronavirus 274 Virus Internalization 100 spike protein, SARS-CoV-2 157

Evidence records

3 total
Functional Mechanism
3 records · 2 evidence types
Evidence type Receptor Usage
1 records
Evidence type Molecular Adaptation
2 records
OVE4898 Molecular Adaptation
Key finding

Specific spike mutations Y144del, 242-244del, K417N/T, E484K, and N501Y in SARS-CoV-2 correspond to neutralization resistance, defining the molecular basis of immune escape.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
Not specified
Location
Not specified
Supporting text

This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2.

Genes or proteins
N-terminal domain | receptor-binding domain (RBD)
Mutations
Y144del | 242-244del | K417N | K417T | E484K | N501Y
Mechanism types
immune escape | receptor binding
OVE4897 Molecular Adaptation
Key finding

SARS-CoV-2 variants B.1.351, P.1, and B.1.1.7 show adaptive resistance to monoclonal antibodies and convalescent plasma, indicating immune escape.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
Not specified
Location
Not specified
Supporting text

Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7.

Genes or proteins
spike protein
Host factors
monoclonal antibodies | convalescent plasma
Mechanism types
immune escape